tbuckley/cabot-search huggingface dataset:
PB2126: RETROSPECTIVE REAL LIFE STUDY OF MULTIPLE MYELOMA STATUS AT DEATH.
Authors: Mónica Fernández Pérez, Ernesto Pérez Persona, Laura Salcedo Cuesta, Xabier Gutierrez Lopez De Ocariz, Jorge Illarramendi Esteban, , Beatriz Larrayoz Sola, Jose Maria Arguinano Perez
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Currently, we have numerous therapeutic options for relapses of multiple myeloma (MM). However, different studies shown an attrition rate of between 21-57% at each line of therapy (LOT), highlighting the use of the most optimal treatment early rather than reserving them for later. Considering that the median age of MM diagnosis is 70 years, we could assume that some MM patients will die due to causes unrelated to MM. Aims: The objective of our study is to analyze the situation of multiple myeloma at the time of patients’ death. Methods: We have included patients diagnosed with MM from 2011 to the present, at Hospital universitario de Alava and Complejo hospitalario de Navarra, who have died at the time of the study and had an available proteinogram in the 3 months prior to death. MM situation has been classified as myeloma in RC (MMrc); MM in progression (MMprog) and MM with active disease (MMad): not included in the above groups. The analysis was made in three groups: Fit: those candidates for TASPE, Intermediate (not candidates for TASPE but <75 years of age) and Elderly (≥75 years of age). In addition, for those patients who died in MMad, death has been classified as: infectious disease (ID), cardiovascular disease (CV), and others (Other). Results: 173 patients meet selection criteria. Overall, 10% of patients have died with MMrc, 39% of patients in MMprog and 51% of patients died in MMad. Considering the patients who died in withing the first 2 LOT, 63% were Elderly, 25% Intermediate, and 13% Fit, while those who died with ≥2 LOT, 38% were Elderly, 32% Intermediate, and 30% fit. Regarding the MM situation at the time of death for each group: Elderly: 11% died in MMrc, 57% in MMad and 32% in MMprog, for the intermediate: 5% in MMrc, 51% in MMad and 44 % in MMprog and for the fit group: 12% in MMrc, 31% in MMad and 58% in MMprogr. Considering cause of death for those in MMad, we observed for the elderly, intermediate and fit patients, 32%, 44% and 50% ID cause of death, respectively, additionally 13% and 10% of the elderly and intermediate patients died because of CV. Summary/Conclusion: In our series, 10% of the patients died in a CR situation, without differences among the three groups. However, 32% of patients ≥75 years died with the disease in progression compared to 58% of those candidates for TASPE. Moreover, up to 27% of the patients died because infection diseases with controlled MM. Not only efficacy, but also safety and tolerance should be taken into consideration for treatment selection, particularly for older MM patients.Keywords: Multiple myeloma, Myeloma
PB2313: THE PROGNOSTIC SIGNIFICANCE OF APOPTOSIS-INDUCING FACTOR IN DIFFUSE LARGE B-CELL LYMPHOMA
Authors: Elena Vaneeva, Vitaliy Rosin, Dmitry Diakonov, Natalia Glubokovskikh
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background:Diffuse large B-cell lymphoma (DLBCL) is the most common variant of non-Hodgkin lymphomas. Approximately 60% of patients achieve complete response (CR) with the standard R-CHOP protocol. One-third of patients develop relapse or refractoriness to therapy. Existing prediction models are often ineffective so searching for additional molecular biological prognostic factors is relevant. Apoptosis-inducing factor (AIF) is a mitochondrial intermembrane space flavoprotein with diverse functions in cellular physiology encoded by the AIFM1 (Xq25) gene. AIF plays role as an effector of the caspase-independent cell death pathway and it also involved in redox reactions. Upon the induction of apoptosis, AIF translocates from the mitochondrial intermembrane space to the nucleus and mediates DNA fragmentation. According to the literature, AIF plays an important role in the pathogenesis of hematological diseases as a proapototic protein. However, the prognostic value of AIF is still unexplored, and the results of studies are inconsistent. Aims:To assess the relationship of AIF protein expression with DLBCL prognosis. Methods:We have analyzed histological slices of formalin-fixed paraffin-embedded (FFPE) tumor tissue samples obtained from 100 patients with newly diagnosed DLBCL. The median age was 58 years. All patients received first-line treatment with R-CHOP regimen. The assessment of the relative number of AIF-positive tumor cells was performed using immunohistochemical and morphometric methods. The median expression of AIF was 60%. According to ROC-analysis threshold value set to 57% AIF-postive tumor cells. All subjects were divided into groups with high (≥57%) and low (<57%) protein expression. The relationship of AIF expression with prognosis in DLBCL was analyzed using univariate Cox regression analysis. Results:AIF expression was detected in 97 out of 100 patients. In 57 subjects, protein expression was found to be above the threshold level, in 43 cases - below the threshold. Low expression of the marker was associated with the lack of a complete response to treatment with R-CHOP regimen (p=0.048), as with III-IV disease stages (p=0.04), higher than normal total serum lactate dehydrogenase (LDH) concentration (p=0.039), IPI ˃2 points (p=0.010). In the studied cohort of patients, with a decrease in the proportion of AIF-positive tumor cells, the risk of an earlier onset of death increased (p=0.04; HR=0.8; 95% CI=0.96-0.99). Summary/Conclusion:A low AIF level is associated with poor clinical diagnostic parameters and a high risk of death in patients with DLBCL. Keywords: Hematological malignancy, B cell, B cell lymphoma, Diffuse large B cell lymphoma
PB2347: THE ROLE OF UPFRONT LENALIDOMIDE MAINTENANCE FOR PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA PATIENTS RESPONDING TO FIRST-LINE MTX TREATMENT
Authors: Yan Zhang, Chao Chen, Danqing Zhao, Zhe Zhuang, Chong Wei, Wei Wang, Wei Zhang, Dao-Bin Zhou
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Consolidation therapy improves duration of response in primary central nerves system lymphoma (PCNSL). Lenalidomide maintenance has shown potential activity in elder adults with PCNSL. However,the efficacy of front-line lenalidomide maintenance in non-elder PCNSL has never been elevated. Aims: We aim to evaluate the effect of lenalidomide maintenance on duration of response in newly-diagnosed PCNSLs Methods: This is a retrospective, single-center analysis. The patients with PCNSL who achieved complete remission or partial remission after high-dose methotrexate induction therapy were enrolled. Lenalidomide maintenance of 25 mg/d was administered orally for 21 days of every 28-day for 24 months in 35 patients, and no further treatment in the observe group. The efficacy and safety data were analysis. Results: 69 patients were enrolled at Peking Union Medical College Hospital from 2003 to 2021. The median age was 58.0 years, and 50.7% (n=35) were male. Patients totaling to 57 (82.6%) achieved CR and 12 (18.4%) achieved PR status. Thirty-five patients received lenalidomide maintenance, the median duration of lenalidomide was 18 (2-36) months. it was well tolerated and barely affected the quality of life. After a median follow-up of 32.6 months, there were less relapsing and death events in the maintenance group. However, the median PFS was similar between groups (36.1months vs 30.6months, HR 0.78, p 0.446), so did median OS (HR 0.4263, p 0.091). In the PR patients after induction, lenalidomide maintenance improved PFS and OS significantly. Summary/Conclusion: This is the first study to compare lenalidomide maintenance with observe as frontline treatment in PCNSL, the improvement of PFS and OS were not observed, although the safety profile was satisfied. Funding: CAMS Innovation Fund for Medical Sciences（CIFMS）2021-I2M-C&T-B-005. Correspondence to: Daobin Zhou, MD Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College No.1 Shuaifuyuan Wangfujing Dongcheng District Beijing, China, 100730 Keywords: Lymphoma therapy, Lymphoma, Non-Hodgkin’s lymphoma
PB1878: MYELOID SARCOMA IN CHILDREN: ABOUT 9 CASES
Authors: Ameni Yahia, Marwa Bahri, Nefzi Rihab, Asma Dhib, Raihane Ben Lakhal, Yosr Ben Abdennabi, Lamia Aissaoui
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: Myeloid sarcoma (MS), also known as granulocytic sarcoma (GS), is a rare tumor mass composed of myeloid blasts that occurs outside of the bone marrow. It can be isolated, but often associated with acute myeloid leukemia (AML).The incidence of MS is higher in pediatric population and it may affect any organ, leading to various clinical presentations. Aims: The objective of this study is to report the clinical features, cytogenetic and molecular characteristics, therapeutic approaches and outcomes of pediatric MS to improve understanding of the disease. Methods: This was a retrospective study that evaluated a series of 9 children diagnosed with MS in hematology pediatric department of Aziza Othmana hospital from January 2006 to December 2022. Results: All patients were Class I-MS given its association with AML (according to the WHO). Among them, 5 patients were LAM2 (56%), 3 patients were LAM5 (33%) and 1 patient was LAM7 (11%). The sex ratio was 2 and the median age at diagnosis was 10 years [2:17]. Organs that were commonly involved in this series were cranial and endocranial sites with extension to the orbital region in 5 cases (56%) and spinal canal in 4 cases (44%). Symptoms of orbital masses were proptosis (4 cases), facial nerve paralysis (1 case), ptosis (1 case) and canthus tumefaction (1 case). Spinal canal myeloid sarcoma was revealed by spinal canal compression in 4 cases. The initial diagnosis was based on Magnetic Resonance Imaging in 6 cases (66%) and only 3 patients were diagnosed by mass biopsy. 8 patients had t(8,21) in karyotype. 6 of them had fusion genes AML1/ETO on molecular testing, cytogenetic and molecular evaluation were not available in other patients. All patients received chemotherapy according to ELAM02 protocol. Only 3 patients received local therapy: 2 decompressive laminectomy and 1 decompressive radiotherapy. All patients had cytologic complete remission of AML in post induction evaluation. However, MS had totally disappeared in 8 patients and one patient had partial regression in post induction evaluation. Prophylactic lumbar puncture was performed for all patients. 3 patients were treated with Allo Hematopoietic Stem Cell Transplantation (HSHCT). Therapy related mortality was 22%: 1 patient died of septic shock during third consolidation, the other one died of toxicity following HSHCT. The 5-year overall survival rate and the 5-year event free-survival rate were 45%.The 5-year free relapse survival rate was 50%. Summary/Conclusion Due to its low incidence, MS is a challenging diagnostic and therapeutic disease and most descriptions of the pathology are case reports. Patients with myeloid sarcoma have usually an unfavorable outcomes. Keywords: Children, Acute myeloid leukemia
PB2263: TOXICITY PROFILE OF SALVAGE CHEMOTHERAPY REGIMENS IN PATIENTS WITH RELAPSED/ REFRACTORY HODGKIN LYMPHOMA.
Authors: Kmira Zahra, Rihab Ben Sghaier, Monia Guermazi, Wafa Chenbah, Nesrine Ben Sayed, Monia Zaier, Yosra Ben Youssef, Haifa Regaieg, Abderrahim Khelif
Journal: HemaSphere (2023)

Topic: 17. Hodgkin lymphoma - Clinical Background: Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard treatment for patients with relapsed/refractory Hodgkin lymphoma (R/R HL). The choice of a salvage treatment protocol should be based on arguments of efficacy (overall response rate), its effectiveness in mobilizing and collecting stem cells, and also on arguments of tolerance (low toxicity). Aims:- Primary objective: assess the toxicity of different salvage chemotherapy (CT) regimens in adult patients with R/R HL. -Secondary objective: compare salvage chemotherapy regimens in order to determine the optimal treatment. Methods: A retrospective study, including 41 patients with R/R HL treated in the Clinical Hematology department between January 2014 and December 2020.The treatment regimens used in our study were DHAP (Dexamethasone-Cytosine arabinoside-Cisplatin), ICE (Ifosfamide-Carboplatin-Etoposide), IGEV (Ifosfamide-Gemcitabine-Vinorelbine) and BVB (BrentuximabVedotin- Bendamustine) followed by ASCT in good responders. Results: The median age was 34 years (18-67 years) with male predominance (sex ratio 1.05). Salvage therapy was indicated for refractory HL in 34 patients (83%) and for relapsed HL in 7 cases (17%). One hundred courses of DHAP were administered in 26 cases: 52 courses were received in 2nd line chemotherapy (CT) in 14 cases and 48 courses in 3rd line CT by 12 patients. The two main toxicities of this regimen were grade 3-4 hematological toxicity (neutropenia, thrombocytopenia) in 30 courses (30%) and grade 3-4 renal toxicity in 3 courses (3%) resulting in the discontinuation of the DHAP. No toxic deaths were reported with DHAP. Ninety-two cycles of IGEV were administered in 25 cases: 89 courses were received in the 2nd line in 24 cases, and 3 courses in the 3rd line in one case. Grade 3-4 thrombocytopenia and neutropenia, infectious toxicity and Grade 1 renal toxicity were seen in 23 (25%), 5 and 1 cycle respectively. Twelve courses of ICE were administered to four patients: 4 as 3rd line in one case and 8 as 4th line in 3 cases. Grade 3-4 hematological toxicity was seen in 2 cycles of ICE (16%). Seventy BVB cycles were received in 14 cases: 14 as 2nd line, 44 as 3rd line and 12 as 4th line. No toxicity was seen. The treatment was discontinued in one case because of death due to disease progression. There was no statistically significant difference in terms of hematological toxicity between DHAP, IGEV and ICE (p=0.286). This may be due to the reduced number of patients. Summary/Conclusion: Compared with DHAP, IGEV and ICE, the BVB regimen has less toxicity in R/R HL. Given the small number of courses more data are needed to confirm these results. Keywords: Hodgkin’s lymphoma, Chemotherapy toxicity, Hematotoxicity
PB2053: POPULATION PHARMACOKINETICS OF PEGCETACOPLAN IN HEALTHY SUBJECTS AND PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
Authors: Haili Ping, Ryan Crass, Sunny Chapel, Temitayo Ajayi
Journal: HemaSphere (2023)

Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical Background: Pegcetacoplan is a PEGylated peptide that targets complement protein C3 and C3b. Aims: A population pharmacokinetic (PK) analysis was performed to describe the serum concentration-time profile of pegcetacoplan and quantify the impact of intrinsic and extrinsic subject factors on its exposure. Methods: Data from 11 clinical studies were used, including 2 phase 3 studies. Pegcetacoplan was administered via subcutaneous (SC) bolus injection, SC delivery devices, or intravenous infusion to healthy adult subjects, adult subjects with renal impairment, or adult patients with paroxysmal nocturnal hemoglobinuria (PNH). Doses ranged from a single 25-mg SC injection to 2600 mg-SC once-weekly infusion; the dosing regimen for phase 3 studies was 1080 mg SC twice weekly (which could be adjusted to every 3 days depending on clinical response) for up to 48 weeks. The final model consisted of 1-compartment systemic disposition, first-order elimination, and transit compartment absorption following SC dose administration. Results: Pegcetacoplan displays linear PKs over the range of doses evaluated in clinical studies. The predicted geometric mean (coefficient of variation %) of clearance is 0.36 L/day (30%) and median (interquartile range) effective elimination half-life is 8.6 (6.9–11.0) days in patients with PNH. Concomitant administration of eculizumab, age, sex, Asian race, Japanese ethnicity, renal function, and hepatic function (as evaluated by total bilirubin, albumin, aspartate aminotransferase, or alanine aminotransferase) had no meaningful effect on the PK profile of pegcetacoplan. Body weight did influence pegcetacoplan kinetics with 1.20-fold (90% CI, 1.16–1.23) higher and 0.827-fold (90% CI, 0.800–0.853) lower average exposure at the 5th (53 kg) and 95th (94 kg) percentiles of body weight compared with a 70-kg reference. Summary/Conclusion: The population PK model adequately described the observed concentration data. Predictions from the model further suggest that no adjustment to initial dosing is needed for the specific populations represented by the intrinsic or extrinsic factors evaluated in this analysis. Keywords: Complement, Population, Paroxysmal nocturnal hemoglobinuria (PNH), Pharmacokinetic
PB2083: IN-VITRO EVALUATION OF LENALIDOMIDE ENANTIOMERS AGAINST HUMAN MULTIPLE MYELOMA CELL LINE
Authors: Gyan Vardhan, Neeraj Jain, Vikas Kumar, Puran Lal Sahu, Ramasare Prasad, Uttam Kumar Nath, Shailendra Handu, Neha Singh, Puneet Dhamija
Journal: HemaSphere (2023)

Topic: 13. Myeloma and other monoclonal gammopathies - Biology & Translational Research Background: The immunomodulatory drugs (IMiDs) have made a profound difference in the treatment of multiple myeloma (MM). Lenalidomide (LND) is chiral compound with two enantiomers and one enantiomer may have different pharmacologic action than the other. For a given chiral drug, until proven otherwise, it is right to think of the two enantiomers as two different drugs with unique properties. Aims: This study aimed to explore efficacy of lenalidomide (R) - (+) and (S) - (-) enantiomers in human multiple myeloma cell line. Methods: H929 myeloma cell line model was designed to understand the potential differences in chirality of the R and S form of LND enantiomers and racemate in multiple myeloma cell line. We report the first biological evaluation of lenalidomide in racemic and in both (R)- and (S)-enantiomerically pure forms against (in vitro) H929 cells of multiple myeloma (MM) using an annexin V assay. Results: It was observed that at 48 hours S-LND treated cells demonstrated significant reduction in the metabolic activity at 10 and 20 µg/mL and profound morphological changes. Cell cycle analysis showed cells in S and G2/M phase were decreased suggesting that all of the drugs can arrest cells at G1 cell cycle phase. We demonstrate (S) - (-) enantiomers of lenalidomide inhibited the growth of H929 MM cells without any in-vivo activation. Summary/Conclusion: The study concludes that (S) - (-) enantiomers of lenalidomide noted more potent agent which could have both the anti-cancerous and immunomodulatory activity.Keywords: Imids, Cell line, Multiple myeloma
PB2355: CORRELATION OF MYD88 AND TNFAIP3 MUTATIONS WITH CLINICO-HEMATOLOGICAL PROFILE IN DIFFUSE LARGE B CELL LYMPHOMA
Authors: Rana Shaat, Hasan A. Abd El Ghaffar, Sameh Shamaa, Hanaa M. Abdel-Masseih, Osama Elbaz
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Activated B-cell–like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) is characterized by chronic active B-cell receptor signaling and a constitutive activation of the nuclear factor kappa B (NF-KB) pathway. As a driving force of NF-KB overactivity, myeloid differentiation primary response gene 88 (MYD88) L265P mutation occurs in ABC-DLBCL. However, the MYD88 L265P mutation has not yet been studied with tumor necrosis factor alpha induced protein3 (TNFAIP3) mutation in DLBCL cases Aims: Determine the prevalence of MYD88 and TNFAIP3 mutations and their relationship with the clinico-hematological profile in DLBCL. Methods: We investigated 100 DLBCL patients for MYD88 L265P and TNFAIP3 mutation by real time polymerase chain reaction Results: MYD88 L265P CT heterozygous genotype was found in 20% of cases. CT heterozygous genotype was significantly frequent in ABC type, stage IV, higher IPI groups, extra-nodal infiltration and BM infiltration. It was also associated with shorter overall survival (OS). TNFAIP3 mutation GA heterozygous genotype was found in 18% of the patients where 77.8% of them were ABC-DLBCL subtype. GA heterozygous genotype was frequently associated with stage IV, and extra-nodal infiltration and shorter OS. Summary/Conclusion: Our study suggests a role of MYD88 mutation in the pathogenesis and prognosis of DLBCL. Keywords: DLBCL, NHL
PB2154: THE IMPACT OF DISEASE SEVERITY ON THE CLINICAL AND ECONOMIC BURDEN OF AL AMYLOIDOSIS
Authors: Anita D’souza, Tiffany Quock, Ansgar Conrad, Michael S. Broder, Ashis K. Das, Eunice Chang, Marian H. Tarbox
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Patients with systemic light chain (AL) amyloidosis often face diagnostic delay, negatively affecting prognosis. Real-world estimates of healthcare resource utilization (HCRU) and costs among patients with AL amyloidosis are limited. Aims: To examine the impact of severity on HCRU and costs in patients with AL amyloidosis. Methods: This retrospective analysis used data from the Merative® MarketScan® Commercial and Medicare Supplemental and the IQVIA Pharmetrics Plus® databases to identify adult patients (existing or newly diagnosed) with ≥1 inpatient or ≥2 outpatient claims for AL amyloidosis (ICD-10-CM code E85.81) in any diagnosis field during 1/1/2019-12/31/2019. Continuous enrollment in a health plan was required. Study outcomes were stratified by severity of AL amyloidosis (defined as the presence of specific cardiac or renal conditions [heart failure, myocardial infarction, chronic kidney disease - stages 4 & 5, pulmonary hypertension, sudden cardiac death/cardiac arrest], or use of cardiac stent or dialysis) and included demographic and clinical characteristics, and HCRU and costs (adjusted to 2020 dollars) during 2019. Results: We identified 343 patients with severe and 248 patients with non-severe AL amyloidosis. Patients with severe AL amyloidosis had more frequent all-cause hospitalizations and emergency department visits than non-severe patients (p<0.001 for both): 51.9% vs. 21.8% and 43.7% vs. 27.0%, respectively. Mean annual number of non-ED outpatient visits (60.6 vs. 33.4), and physician office visits (23.3 vs. 17.4) were higher in patients with severe AL amyloidosis (all p<0.001). Mean (standard deviation) all-cause and AL-specific healthcare costs were significantly greater (p<0.001) among patients with severe AL amyloidosis than in non-severe patients ($192,881 [200,713.3] vs. $91,171 [121,679.2]; $92,771 [136,368.5] vs. $49,829 [89,492.6]). Summary/Conclusion: Patients with severe AL amyloidosis had greater HCRU and cost burden than patients with non-severe AL amyloidosis. Effective disease management and additional treatment options are necessary to reduce disease progression and subsequent higher HCRU and costs. Keywords: Treatment, Real world data, AL amyloidosis, Bortezomib